Phenyl carbamate compounds for use in preventing or treating a movement disorder

Abstract

The present invention provides a pharmaceutical composition for preventing and/or treating a movement disorder comprising the phenyl carbamate compound as an active ingredient, and a use of the phenyl carbamate compound for preventing and/or treating movement disorder.

What is claimed is: 
     
       1. A method of treating a movement disorder in a subject in need thereof, the method comprising administering a therapeutically effective amount of a pharmaceutical composition to the subject, the composition comprising a compound of Formula 1 or pharmaceutically acceptable salt thereof as an active ingredient: 
       
         
           
           
               
               
           
         
         wherein,
 X is a halogen, 
 n is the number of X substituents and is an integer from 1 to 5, 
 R 1  is a linear or branched C 1 -C 4  alkyl group, 
 A is hydrogen or a carbamoyl group represented by 
 
       
       
         
           
           
               
               
           
         
         
           B is hydrogen, a carbamoyl group represented by 
         
       
       
         
           
           
               
               
           
         
         
            trialkyl silyl, trialkylaryl silyl, or a trialkyl silyl ether, wherein each alkyl is independently a linear, branched, or cyclic C 1 -C 4  alkyl, and each aryl is independently a C 5 -C 8  aryl, and 
           R 2  and R 3  are the same as or different from each other, and independently a hydrogen, a linear or branched C 1 -C 4  alkyl, a C 3 -C 8  cycloalkyl, or benzyl, 
         
         wherein when A is hydrogen, B is a carbamoyl group, or when A is a carbamoyl group, B is hydrogen; 
         wherein the compound is in the form of a racemate, enantiomer, diastereomer, a mixture of enantiomer, or mixture of diastereomers; 
         and wherein the movement disorder is dyskinesia, dystonia, tremors, essential tremor, Parkinsonian tremor, multiple system atrophy, myoclonus, Parkinson's disease, progressive supranuclear palsy, restless legs syndrome, Rett syndrome, Sydenham's chorea, other choreas, athetosis, ballism, stereotypy, tardive dyskinesia/dystonia, tics, Tourette's syndrome, olivopontocerebellar atrophy (OPCA), hemibalismus, hemi-facial spasm, Wilson's disease, stiff man syndrome, akinetic mutism, psychomotor retardation, painful legs moving toes syndrome, a gait disorder, or a drug-induced movement disorder. 
       
     
     
       2. The method according to  claim 1 , wherein X is chlorine, fluorine, iodine, or bromine; n is 1 or 2; and R2 and R3 are the same as or different from each other, and independently hydrogen, methyl, propyl, isopropyl, cyclopropyl, cyclohexyl, bicycloheptane, or benzyl. 
     
     
       3. The method according to  claim 1 , wherein the compound is
 1-(2-chlorophenyl)-1-hydroxypropyl-2-carbamate, 
 1-(2-chlorophenyl)-1-hydroxy-3-methyl-butyl-2-carbamate, 
 1-(2-chlorophenyl)-1-hydroxyhexyl-2-carbamate, 
 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-methylcarbamate, 
 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-propylcarbamate, 
 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-isopropylcarbamate, 
 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-cyclopropylcarbamate, 
 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-cyclohexylcarbamate, 
 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-benzylcarbamate, 
 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-bicyclo[2,2,1]heptanecarbamate, 
 1-(2,4-dichlorophenyl)-1-hydroxypropyl-2-carbamate, 
 1-(2,6-dichlorophenyl)-1-hydroxypropyl-2-carbamate, 
 1-(2,4-dichlorophenyl)-1-hydroxybutyl-2-carbamate, 
 1-(2,4-dichlorophenyl)-1-hydroxy-3-methyl-butyl-2-carbamate, 
 1-(2,6-dichlorophenyl)-1-hydroxy-3-methyl-butyl-2-carbamate, 
 1-(2,4-dichlorophenyl)-1-hydroxyhexyl-2-carbamate, 
 1-(2,6-dichlorophenyl)-1-hydroxyhexyl-2-carbamate, 
 1-(2-chlorophenyl)-2-hydroxypropyl-1-carbamate, 
 1-(2-chlorophenyl)-2-hydroxypropyl-1-N-methylcarbamate, 
 1-(2-chlorophenyl)-2-hydroxypropyl-1-N-propylcarbamate, 
 1-(2-chlorophenyl)-2-hydroxypropyl-1-N-isopropylcarbamate, 
 1-(2-chlorophenyl)-2-hydroxypropyl-1-N-cyclopropylcarbamate, 
 1-(2-chlorophenyl)-2-hydroxypropyl-1-N-cyclohexylcarbamate, 
 1-(2-chlorophenyl)-2-hydroxypropyl-1-N-benzylcarbamate, 
 1-(2,4-dichlorophenyl)-2-hydroxypropyl-1-carbamate, 
 1-(2,6-dichlorophenyl)-2-hydroxypropyl-1-carbamate, 
 1-(2,4-dichlorophenyl)-2-hydroxybutyl-1-carbamate, 
 1-(2,6-dichlorophenyl)-2-hydroxybutyl-1-carbamate, 
 1-(2,4-dichlorophenyl)-2-hydroxy-3-methyl-butyl-1-carbamate, 
 1-(2,6-dichlorophenyl)-2-hydroxy-3-methyl-butyl-1-carbamate, 
 1-(2,4-dichlorophenyl)-2-hydroxyhexyl-1-carbamate, 
 1-(2,6-dichlorophenyl)-2-hydroxyhexyl-1-carbamate, 
 1-(2-fluorophenyl)-1-hydroxypropyl-2-carbamate, 
 1-(2-iodophenyl)-1-hydroxypropyl-2-carbamate, 
 1-(2-iodophenyl)-1-hydroxybutyl-2-carbamate, 
 1-(2,3-dichlorophenyl)-1-hydroxypropyl-2-carbamate, or 
 1-(2,3-dichlorophenyl)-2-hydroxypropyl-1-carbamate, 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
       4. The method according to  claim 1 , wherein the compound is
 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate, 
 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-carbamate, 
 racemate of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate and 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-carbamate, 
 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(S)-2-carbamate, 
 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(R)-2-carbamate, 
 1-(2-chlorophenyl)-(S)-1-hydroxybutyl-(S)-2-carbamate, 
 racemate of 1-(2-chlorophenyl)-(S)-1-hydroxybutyl-(S)-2-carbamate and 1-(2-chlorophenyl)-(R)-1-hydroxybutyl-(R)-2-carbamate, 
 1-(2-chlorophenyl)-(S)-1-hydroxy-3-methyl-butyl-(S)-2-carbamate, 
 racemate of 1-(2-chlorophenyl)-(S)-1-hydroxy-3-methyl-butyl-(S)-2-carbamate and 1-(2-chlorophenyl)-(R)-1-hydroxy-3-methyl-butyl-(R)-2-carbamate, 
 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-methylcarbamate, 
 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-propylcarbamate, 
 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(R)-2-N-isopropylcarbamate, 
 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(R)-2-N-cyclopropylcarbamate, 
 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(R)-2-N-cyclohexyl carbamate, 
 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-methylcarbamate, 
 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-propylcarbamate, 
 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-isopropylcarbamate, 
 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-cyclopropylcarbamate, 
 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-cyclohexyl carbamate, 
 racemate of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-methylcarbamate and 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-methylcarbamate 
 racemate of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-propylcarbamate and 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-propylcarbamate, 
 racemate of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-isopropylcarbamate and 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-isopropylcarbamate, 
 racemate of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-cyclopropylcarbamate and 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-cyclopropylcarbamate, 
 racemate of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-cyclohexylcarbamate and 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-cyclohexylcarbamate, 
 1-(2-fluorophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate, 
 1-(2-fluorophenyl)-(R)-1-hydroxypropyl-(R)-2-carbamate, 
 1-(2-iodophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate, 
 1-(2-iodophenyl)-(R)-1-hydroxypropyl-(R)-2-carbamate, or 
 1-(2-iodophenyl)-(S)-1-hydroxybutyl-(S)-2-carbamate, 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
       5. The method according to  claim 1 , wherein the movement disorder is tremors, essential tremor, Parkinsonian tremor or Parkinson's disease.